We discuss a general thermodynamic analysis of the complex formation between proteins and polyelectrolytes. This analysis allows us to quantify the main driving forces, namely counterion release and hydration.[1] In particular, the analysis of hydration effects leads to a quantitative understanding of the Hofmeister-effects on the interaction of polyelectrolytes with proteins.[2] In my talk I will discuss this model and its application to biocondensates, that is, the phase separation in mixtures of proteins of opposite charge. In particular, I will present the analysis of the binary complex formation of the highly positively charged linker histone H1 and the highly negatively charged chaperone, prothymosin α (ProTα). ProTα and H1 have large opposite net charges (−44 and +53, respectively) and form complexes at physiological salt concentrations with high affinity as shown by Chowdhury et al.[3] The analysis demonstrates that the release of the counterions mainly bound to ProTa is the main driving force, hydration effects related to water release play no role within the limits of error. A strongly negative Dcp (= -0.87 kJ/(K mol)) is found which is due to the loss of conformational degrees of freedom.[4] The entire analysis demonstrates the basic importance of charge-charge interaction in biologically relevant systems.
References
[1] J. J. Walkowiak, M. Ballauff, Adv Sci 2021, 8, 2100661.
[2] W. Malicka, R. Haag, M. Ballauff, J Phys Chem B 2022, 126, 6250-6260.
[3] A. Chowdhury, A. Borgia, S. Ghosh, A. Sottini, S. Mitra, R. S. Eapen, M. B. Borgia, T. Yang, N. Galvanetto, M. T. Ivanovic, P. Lukijanczuk, R. Zhu, D. Nettels, A. Kundagrami, B. Schuler, Proc Natl Acad Sci U S A 2023, 120, e2304036120.
[4] M. Ballauff, Biomolecules 2024, 14.